1. Field of the Invention
The present invention relates to a percutaneous absorption preparation which enables stable administration of an antidementia drug over a long period of time.
2. Background Art
Recently, dementia patients with Alzheimer's type have been increased with population growth of seniors, and the care of patients becomes a serious social problem. On the other hand, antidementia drugs have rapidly been developed, and for example donepezil hydrochloride has extensively been used as a remedy against Alzheimer's disease which has acetylcholinesterase inhibitory effect. Hitherto, these antidementia drugs have mostly been administered orally in the form of tablets. Drugs are administered to patients in the form of tablets, capsules, syrups, granules as well as via injection, rectal dosage, and the like, which are appropriately chosen depending on diseases or the property of the drugs.
However, it is often hard for a dementia patient in an advanced stage to take an antidementia drug. Therefore, the transdermal administration of the antidementia drug is believed very useful in administering the drug continuously for a long period without difficulty in taking the drug.
However, it is generally considered that poor permeability of a drug to skin leads to the difficulty of absorbing the drug in an amount sufficient to exert effect into body through the skin. Percutaneous absorption preparations for antidementia drugs have hitherto been examined in order to get over the difficulty.
For example, Japanese Patent Laid-Open Publication No. 1998/315016 (JP 11-315016A) discloses an ointment for the percutaneous administration of antidementia drug or a suppository for the rectal administration of the drug and it is reported that the percutaneous absorbability of donepezil is enhanced with use of base material containing a higher alcohol and an ester derivative thereof.
Further, WO 03/032960 discloses a percutaneous absorption preparation for the treatment of dementia, the preparation comprising an adhesive composition, the adhesive composition containing an active ingredient dispersed therein, the active ingredient being released at a pharmacologically effective rate, and the skin permeation rate thereof being 1.2 μg/cm2/hour or more. In addition, Example discloses an adhesive composition containing preparation which comprises a donepezil hydrochloride as the active ingredient, a styrene-isoprene-styrene block copolymer as the hydrophobic polymer, and sodium acetate as the organic acid salt, and the size of the preparation for a single dosage for 24 hours is regarded as 60 cm2.
Furthermore, it is required for a percutaneous absorption preparation that the drug as the active ingredient is maintained without deposition in the preparation and placed stably on the skin. Thus, the percutaneous absorption preparation and its materials have been examined in consideration of the improvement of these functions.
For example, Japanese Patent Laid-Open Publication No. 1998/182439 (JP 10-182439A) discloses an adhering and joining agent for skin or transdermal treatment systems, which comprises a (meth)acrylate copolymer containing a tertiary or quaternary amino group, an acidic group-containing acrylate or (meth)acrylate polymer or copolymer, and a plasticizer. Example of the publication discloses triethyl citrate and acetyl triethyl citrate as the plasticizer.
Also, WO 02/38139 discloses a percutaneous absorption preparation comprising an aminated polymer, a drug in the form of an acid addition salt, and a carboxylic acid and/or a salt thereof.
In addition, Japanese Patent Laid-Open Publication No. 1992/117323 (JP 04-117323A) discloses a percutaneous absorption preparation which maintains a adhesive layer containing a drug on a backing layer, characterized in that the percutaneous absorption preparation contains a certain amount of a drug in the form of an acid addition salt and a polymer containing a certain amount of a basic nitrogen and having no tackiness to skin at ordinary temperature.
However, when the antidementia drug is intended to administer to a patient for a long period, for example one week or so, it is still difficult to stably hold the preparation on the skin and continuously release the antidementia drug from the preparation. Thus, it can be said that a percutaneous absorption preparation of an antidementia drug which has both stable drug releasability and adhering ability to skin suitable for the administration of the drug for a long period is still needed.